Clin Res Cardiol
DOI 10.1007/s00392-015-0859-7
REVIEW
The importance of sleep-disordered breathing in cardiovascular
disease
Dominik Linz1 • Holger Woehrle2 • Thomas Bitter3 • Henrik Fox3
Martin R. Cowie4 • Michael Böhm1 • Olaf Oldenburg3
Received: 4 February 2015 / Accepted: 15 April 2015
Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Obstructive sleep apnoea and central sleep ap-
noea/Cheyne-Stokes respiration are collectively referred to
as sleep-disordered breathing (SDB). Rapidly accumulat-
ing evidence suggests that both forms of SDB, and often a
combination of both, are highly prevalent in patients with a
wide variety of cardiovascular diseases, including hyper-
tension, heart failure, arrhythmias, coronary artery disease,
acute coronary syndrome and stroke. The presence of SDB
in these patients is independently associated with worse
cardiac function and exercise tolerance, recurrent arrhyth-
mias, infarct expansion, decreased quality of life and in-
creased mortality. Recent data suggest positive effects of
positive airway pressure (PAP) therapy on quality of life
and cardiovascular function. In addition, ongoing clinical
trials may soon provide first definitive data on PAP therapy
of SDB on hard outcomes such as mortality. This review
presents current data highlighting links between SDB and a
variety of cardiovascular conditions, the importance of
recognising and diagnosing SDB in patients with cardio-
vascular disease, and the effects of effective SDB treatment
on cardiovascular endpoints.
& Dominik Linz
dominik.linz@uks.eu
1
Kardiologie, Angiologie und Internistische Intensivmedizin,
Klinik für Innere Medizin III, Universitätsklinikum des
Saarlandes, Kirrberger Strasse 1, Geb. 40, 66421 Homburg,
Saarland, Germany
2
ResMed Science Centre, ResMed Europe, Munich, Germany
3
Heart and Diabetes Center North Rhine-Westphalia, Ruhr
University Bochum, Bad Oeynhausen, Germany
4
Faculty of Medicine, National Heart and Lung Institute,
Imperial College London, London, England, UK
•
Keywords Obstructive sleep apnoea
Central sleep
apnoea
Cheyne-Stokes respiration
Cardiovascular
disease
Atrial fibrillation
Mortality
Introduction
Sleep-disordered breathing (SDB), or sleep apnoea, is a
highly prevalent co-morbidity in cardiovascular diseases
(CVD) with an independent negative impact on patient
quality of life and is associated with high healthcare costs
[1–7]. However, the importance of SDB in cardiology goes
beyond symptoms of unrestful sleep, particularly in pa-
tients with CVD. There are a number of factors that
combine to compel cardiologists to pay more attention to
sleep-related breathing disorders, like the high prevalence
of SDB in patients with CVD (Fig. 1) [1, 3–7], the possible
impact of SDB on the underlying disease, the availability
of different strategies to diagnose and treat SDB, and the
promising effects associated with treating SDB in patients
with CVD.
What is sleep-disordered breathing?
There are three basic mechanisms for the disruption of
respiration during sleep: upper airway obstruction, dys-
regulation of respiratory control, and hypoventilation [8].
Two main breathing abnormalities predominating in SDB
are obstructive sleep apnoea (OSA) and central sleep ap-
noea (CSA), which may manifest as Cheyne-Stokes res-
piration (CSR). Disease severity is determined by the
number of respiratory events per hour of (estimated) sleep
time [the apnoea–hypopnoea index (AHI)], and the number
and severity of oxygen desaturations [9]. SDB is usually
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Fig. 1 Prevalence of SDB in
patients with coronary heart
disease, hypertension, chronic
heart failure, atrial fibrillation,
and resistant hypertension [1, 3,
5–7] with respective definition
of sleep apnoea [apnoea-
hypopnoea index (AHI)]
defined as mild if the AHI is 5–15/h, moderate when AHI is
15–30/h and severe when the AHI is [30/h.
Obstructive sleep apnoea (OSA)
Obstructive sleep apnoea is the most common type of SDB
in the general population and is characterised by recurrent
partial (hypopnoea) or complete (apnoea) collapses of the
upper airway during sleep, even when there is respiratory
effort (Fig. 2). Typical clinical symptoms of OSA in pa-
tients without CVD include excessive daytime sleepiness,
insomnia, morning headaches, depression, cognitive dys-
function, nocturnal dyspnoea, nocturia, erectile dysfunction
and drowsy driving. However, there is wide inter-indi-
vidual variation in symptoms, especially between male and
female patients [9]. Women tend to have less severe OSA
and a lower AHI than males, partly due to episodes of
Fig. 2 Pathophysiology of obstructive (OSA) and central sleep
apnoea (CSA) and the effect on the heart
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Clin Res Cardiol
upper airway resistance and flow limitation that do not
meet the criteria for apnoeas. This may contribute to the
lower rate of SDB diagnosis in women. Other factors im-
plicated in gender-related SDB variation are differences in
the upper airways, fat distribution and respiratory stability,
and changes in hormones. These differences between men
and women appear to decrease as age increases. Further-
more, changes in airway and lung function during preg-
nancy may contribute to snoring and OSA [9].
At least, 50 % of patients with severe OSA do not report
symptoms of unrestful sleep. This proportion is even higher
in patients with OSA and CVD, who often primarily report
symptoms of underlying CVD rather than typical signs of
OSA [10, 11].
The gold standard therapy for OSA is continuous posi-
tive airway pressure (CPAP), which splints the upper air-
way and maintains upper airway patency, thus alleviating
obstructive respiratory events [12] (Fig. 3). Additional
beneficial cardiovascular effects of CPAP include in-
creased intrathoracic pressure, reduced left ventricular pre-
and afterload, and reduced transmural cardiac pressure
gradients, all of which can ameliorate impaired cardiac
function [13, 14]. Long-term compliance with CPAP
therapy in symptomatic OSA patients is good, with about
70 % still regularly using treatment after 5 years [15]. In
OSA patients who are unable to tolerate CPAP therapy, an
effective alternative approach is the use of a mandibular
repositioning device [16, 17].
Central sleep apnoea/Cheyne-Stokes respiration
(CSA/CSR)
Central sleep apnoea and Cheyne-Stokes respiration are
mediated by a dysregulation of respiratory control. Heart
failure (HF) is the most obvious cause of CSA/CSR, but it
has also been observed in patients with stroke, especially in
the acute phase, and in those with renal failure [18]. CSR is
characterised by periodic episodes of hyper- and hy-
poventilation, with a typical waxing and waning pattern
[19] (Fig. 2). This form of SDB is associated with chronic
Clin Res Cardiol
Fig. 3 Different treatments for SDB: a continuous positive airway
pressure (CPAP): fixed or automatically adjusted expiratory pressure
(EPAP). CPAP aims to maintain upper airways open. b Bilevel
positive airway pressure (BiPAP): fixed EPAP and pressure support
(PS) at inspiration [inspiratory pressure (IPAP)], usually with fixed
backup rate. BiPAP aims to trigger breathing in respiratory
hyperventilation and patients usually have low carbon
dioxide (CO2) levels. Dysregulation of respiratory control
is mediated by increased sensitivity of peripheral and
central chemoreceptors [19]. Other contributing factors are
pulmonary congestion and prolonged circulation time [19].
Interestingly, CSR is not just limited to sleep but can also
occur at rest and during exercise in patients with advanced
HF [20, 21]. The cycle length of CSR in HF is related to
reduction in cardiac function [22]. It has been suggested
that CSR with associated hyperventilation may be a com-
pensatory mechanism that has detrimental effects in HF
[23].
Standard management of CSA/CSR in CVD patients
consists of optimising treatment for the underlying disease,
especially HF. Effective pharmacological and device
therapy has been shown to significantly improve the
severity of CSA/CSR in patients with HF [24–27], and
heart transplantation may eliminate CSA/CSR. A number
of treatments for CSA/CSR have been studied, including
oxygen, carbon dioxide, CPAP, bilevel positive airway
pressure (BiPAP) and adaptive servoventilation (ASV)
(Fig. 3). Oxygen therapy has been the subject of a few
small-scale trials. Its use during sleep reduces the severity
of CSA/CSR by approximately 50 %, but only one study
has reported clinical improvements [28]. Administration of
carbon dioxide reduces AHI, but at the expense of
insufficiency. c Adaptive servoventilation (ASV): fixed or auto-
matically adjusted expiratory pressure [minimal (EPAPmin) and
maximal (EPAPmax)] and adaptive pressure support [minimal (PSmin)
and maximal (PSmax)] at inspiration with servo controlled backup
rate. ASV aims to stabilise all form of unstable breathing such as
CSA/CSR
hyperventilation and poor sleep quality, and is not used
clinically [29]. Although it does not trigger inspiration
during central apnoea, CPAP improves CSA/CSR probably
by increasing functional residual capacity (and, as a result,
oxygen stores), decreasing blood volume in the lungs and
upper airway when lying down [30], and reducing hyper-
ventilation via a direct effect on the paravasal J-receptors
of the lung [31]. In addition, CPAP reduces pre- and
afterload and the cardiac transmural pressure [32]. How-
ever, not all patients respond to CPAP therapy, for exam-
ple, due to unresolved mask leaks or unsatisfactory positive
airway pressure titration. Some patients even develop CSR
during CPAP administration, a finding labelled as complex
sleep apnoea [8, 33, 34]. BiPAP with backup rate has been
shown to be more effective than CPAP at controlling CSA/
CSR [35], but it can also worsen central SDB [36]. This is
because BiPAP with backup rate is designed to provide
ventilation and reduce CO2 levels, which does not ame-
liorate the hyperventilation and low CO2 levels associated
with CSA/CSR. For this reason, BiPAP is not considered
an adequate treatment for CSA/CSR.
ASV is the most effective treatment for SDB in heart
failure patients, providing the best control of nocturnal
respiratory events [37]. The advantage of ASV compared
to other SDB treatment options is that it treats both OSA
and CSA/CSR. ASV ensures upper airway patency using a
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fixed or varied amount of expiratory positive airway
pressure, while a varying amount of inspiratory pressure
support sustains inspiration with decreasing breathing
amplitude or even ensures inspiration with sustained
breathing efforts [37, 38]. Thereby, ASV also uses a
‘backup rate’, which acts as a respiratory pacemaker during
apnoeas. Treatment with ASV can effectively suppress
complex sleep apnoea and has positive effects on cardiac
function and respiratory stability [33]. Phrenic nerve
stimulation is a new approach to the treatment of CSA/
CSR, with initial results showing that it may improve
central respiratory events by about 50 % [39–41].
Physiological effects of sleep-disordered breathing
In OSA, attempts to breath against the occluded upper
airways not only result in acute hypoxaemia and hyper-
capnia, but also in profound negative intrathoracic pressure
swings, which increase cardiac transmural pressure gradi-
ents [29], sympathetic activation [42], impairment of ven-
tricular mechanics [43], arousals, and sleep fragmentation
and deprivation [44]. Additionally, in the long run, these
processes could lead to structural and functional remod-
elling processes in the heart and may contribute to the
development and progression of CVD in the context of
OSA [44] (Fig. 4).
Like OSA, CSA/CSR results in desaturations and
arousals, activating the sympathetic nervous system [9],
which can lead to progression and deterioration of under-
lying CVD. In contrast, intrathoracic pressure swings and
subsequent changes in transmural pressure are not observed
in CSA/CSR. CSR has been shown to be an independent
predictor of increased mortality in patients with HF and
impaired left ventricular ejection fraction (LVEF) [45, 46].
Sleep-disordered breathing and hypertension
The potential role of OSA in the pathogenesis of hyper-
tension has been recognised in international guideline
documents [47–49]. Approximately, half of all patients
with OSA have hypertension and about 30–40 % of pa-
tients with arterial hypertension also have clinically rele-
vant OSA [9]. The prevalence is even higher (up to 90 %)
in those with drug-resistant hypertension [5, 50, 51]. Co-
hort study data suggest that the risk and prevalence of
hypertension increase as the severity of OSA increases
[52–59]. CPAP alleviates intermittent hypoxia and reduces
sympathetic drive in OSA patients and thus lowers blood
pressure during sleep [42]. In patients with cardiovascular
disease or multiple cardiovascular risk factors, the treat-
ment of OSA with CPAP, but not nocturnal supplemental
oxygen, resulted in a significant reduction in blood pressure
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Clin Res Cardiol
[60]. This suggests that it is not just intermittent hypoxia
alone but factors directly associated with obstructive res-
piratory events that are the relevant trigger for hyperten-
sion. Compared to intermittent apnoea alone, obstructive
respiratory events are associated with apnoea associated
changes in renal perfusion and subsequent sympathetic and
neurohumoral activation which may contribute to the
pathophysiology of OSA-associated hypertension [61].
Randomised clinical trials have assessed the effects of
CPAP treatment on OSA in more than 1600 patients with
hypertension [62]. In the majority of studies, the effect of
treatment on BP has been favourable. The results of two
meta-analyses, including studies that were conducted
largely in normotensive patients, suggest that the reduction
in BP during CPAP therapy in patients with OSA is in the
region of 1.5–2.5 mmHg [63, 64]; the magnitude of effect
varied from nothing up to a 10 mmHg reduction in BP [65,
66]. Regression analysis estimated that 24-h mean BP
would decrease by 1.39 mmHg for each 1-h increase in
effective nightly use of a CPAP device [64]. In the most
recent meta-analysis of published data, which included 32
randomised controlled trials, mean reductions in daytime
systolic and diastolic BP with CPAP versus no treatment
were 2.6 and 2.0 mmHg, respectively; corresponding night-
time reductions were 3.8 and 1.8 mmHg [67]. The magni-
tude of BP reductions during CPAP therapy was at least half
that attributed to antihypertensive drugs in similar analyses.
Another interesting finding of this systematic review was
that there was a link between baseline OSA severity and the
beneficial effects of CPAP on BP—the higher the baseline
AHI, the greater the reduction in systolic BP—suggesting
that patients with more severe OSA may benefit the most
from CPAP therapy in terms of BP reduction [67].
The greatest benefits of CPAP therapy for OSA have
been seen in patients with difficult-to-treat hypertension [5,
50, 51, 68]. In patients with resistant hypertension, treat-
ment of OSA with CPAP reduced daytime BP by
6.5 mmHg, compared with a 3.1 mmHg increase in un-
treated patients over the study period [51]. It is important to
mention that compliance to CPAP therapy by patients with
resistant hypertension plays a key role in achieving optimal
BP reduction. Decreases in 24-h BP were documented in
patients with resistant hypertension who used CPAP for
[5.8 h per night, but not in those with lower usage [68],
and another study of CPAP treatment for OSA in patients
with resistant hypertension reported a significant correlation
between hours of CPAP use and decreases in 24-h systolic
and diastolic BP [69]. Other factors influencing the mag-
nitude of the effect of CPAP on BP include sleepiness
symptoms, severity of desaturations, compliance with
CPAP therapy, and pharmacological pre-treatment [70, 71].
The evidence described above and the document anti-
hypertensive effects of CPAP therapy in OSA patients
Clin Res Cardiol
Fig. 4 Links between sleep
apnoea and cardiovascular
disease (adapted from Somers
et al. [10]). SA sleep apnoea
indicate that SDB is a relevant cause of hypertension. For
clinical practice, it is important to mention that it takes
3–6 months to achieve the maximum reduction in BP as-
sociated with CPAP therapy [70]. OSA is recognised as
the most prevalent risk factor contributing to resistant
hypertension [72], and an American Heart Association
(AHA) scientific statement recommends that OSA in pa-
tients with resistant hypertension should be treated with
CPAP [73].
Sleep-disordered breathing and heart failure
The Sleep Heart Health Study identified OSA as an inde-
pendent risk factor for the development of HF [74], with
more impact in men than in women [75]. The prevalence of
SDB in patients with HF with preserved ejection fraction
(HFpEF) or HF with reduced ejection fraction (HFrEF) is
up to 70 and 76 %, respectively [76, 77], and 45–50 % of
these have moderate-to-severe SDB [77]. OSA appears to
be the predominant SDB in patients with HFpEF, with a
prevalence of 62 % compared with 18 % for CSA [78].
Conversely, the prevalence of CSA/CSR in patients with
HFrEF is high [79]. The severity of ventricular dysfunction
is driving the risk for CSA/CSR and with increasing im-
pairment in cardiac function, there is an increase in CSA/
CSR prevalence [18] (Fig. 5).
In patients with HF and impaired LVEF, untreated OSA
and CSA are independent risk factors for a worse prognosis
and death [46, 80–82], and daytime CSR is a significant
independent predictor of mortality in patients with severe
congestive HF [83]. Even when treatment of HF is opti-
mised, persistent low levels of CSA/CSR or OSA appear to
have an important negative impact on prognosis [84].
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Fig. 5 Scheme of the relative prevalence of obstructive (OSA) and
central sleep apnoea (CSA) according to heart failure severity. With
increasing impairment in cardiac function there is an increase in CSA
prevalence. NYHA New York Heart Association class (adapted from
Oldenburg et al. [18])
It is important to note that HF patients with SDB do not
usually have typical symptoms, such as daytime sleepiness
[3, 10, 85, 86]. This may be the result of increased sym-
pathetic nervous system activity secondary to SDB that
stimulates alertness and counteracts the effects of sleep
fragmentation and deprivation [87].
Two randomised trials evaluating the effect of CPAP
therapy in patients with OSA and HF showed significant
improvements in LVEF after 1 and 3 months [88, 89]. In
addition, quality of life was improved and sympathetic
activity was reduced. A Japanese cohort study documented
a positive effect of CPAP treatment on survival in HF
patients with OSA, although this was not a randomised
controlled trial, and also highlighted the importance of
compliance with therapy in achieving beneficial outcomes
[90]. Treating newly diagnosed OSA with CPAP in men
without overt cardiovascular disease was associated with
improvements in echocardiographic markers of diastolic
function [91].
The 2010 Heart Failure Society of America Compre-
hensive Heart Failure guidelines recommend screening for
SDB and CPAP therapy in those with confirmed OSA [92].
The 2013 ACCF/AHA guidelines acknowledge that treat-
ing OSA with CPAP in patients with HF does have benefit
[93].
Use of CPAP has been shown to alleviate CSA/CSR in
patients with HF [14, 30, 94, 95]. Improvements associated
with CPAP therapy include a decreased number of CSA
episodes, improved oxygenation, increased LVEF, de-
creased noradrenaline levels and improved 6-min walk
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Clin Res Cardiol
distance [96]. Nevertheless, the Canadian Positive Airway
Pressure (CANPAP) study, which investigated the effect of
CPAP therapy of CSA/CSR in patients with stable HF on
transplantation-free survival, did not show a positive effect
of treatment on either transplant-free survival or hospi-
talisation [96]. The trial was stopped prematurely after a
prespecified interim analysis for a number of reasons, in-
cluding decline in event rate, low recruitment and early
increase in mortality in the CPAP group. A post hoc ana-
lysis of the CANPAP data suggested that patients who
achieved normalisation of respiratory events during PAP
therapy may have improved outcomes [97].
Data from studies such as CANPAP indicate that ef-
fective control of SDB may be important for improving
morbidity and mortality in patients with CSA/CSR. How-
ever, a high proportion of patients with CSA have residual
apnoea events despite CPAP therapy, suggesting that a
more effective intervention is required [98].
ASV has been shown to be the most effective inter-
vention for controlling SDB in patients with HF [37].
Smaller trials have documented improvements in AHI,
sleep quality, quality of life, LVEF, New York Heart As-
sociation class, oxygen uptake, natriuretic peptides, in-
flammatory markers and exercise capacity [99–104], and a
meta-analysis provides an overview of the treatment effect
[105].
In randomised, controlled clinical trials, beneficial ef-
fects of ASV treatment of CSA/CSR in HF patients include
significant reductions in AHI [106–111], N-terminal pro-
BNP levels [107, 110–113], urinary catecholamine release
[110] and left ventricular end-systolic diameter [107], in-
creases in 6-min walk distance [107] and LVEF [106, 108,
109], and improved NYHA class [108].
ASV has been shown to be more effective than BiPAP
for treating CSA/CSR in HF [114] and ASV is better tol-
erated than CPAP [115], resulting in improved compliance
with therapy, which is an important part of successful
treatment [107].
The effect of ASV treatment on morbidity and mortality
is currently being investigated in the SERVE-HF and
ADVENT-HF trials (clinicaltrials.gov identifier:
NCT00733343 and NCT01128816). The SERVE-HF has
enrolled approximately 1325 patients with chronic stable
HFrEF and CSA/CSR, with an expected finish date of mid-
2015 [116]. The Cardiovascular Improvements With Min-
ute Ventilation-targeted ASV Therapy in Heart Failure
(CAT-HF) study (clinicaltrials.gov identifier:
NCT01953874) will compare the effects of targeted ASV
added to optimised medical therapy compared with medi-
cal therapy alone in patients with acute decompensated HF.
The primary outcome is a global measure combining sur-
vival free from cardiovascular hospitalisation and im-
provement in functional capacity; changes in functional
Clin Res Cardiol
parameters, biomarkers, quality of life and sleep-disor-
dered breathing will also be assessed.
Another area of interest is the use of ASV in patients
with HFpEF and CSA/CSR. Early results show that ASV
can improve cardiac diastolic function, improve symptoms
and decrease brain natriuretic peptide levels in this group
of patients [117, 118]. In addition, the proportion of HFpEF
patients treated with ASV who were free of cardiac events
was significantly higher than that in untreated patients
[118].
Sleep-disordered breathing and cardiac
arrhythmias
Atrial fibrillation
Sleep apnoea is highly prevalent in patients with AF. More
than 50 % of those with paroxysmal AF and a high AF
burden or persistent AF have been shown to have clinically
relevant SDB [7]. The prevalence of CSA in patients with
AF is not well described and few data are currently avail-
able. One study has reported a high proportion of CSA
(79 %) in a group of pacemaker recipients with permanent
AF [76]; this was probably a result of a high rate of HF and
depressed LVEF in this study population. Another study in
AF patients with normal left ventricular function showed
prevalence rates of 31 % for CSA/CSR and 43 % for OSA
[119]. Several mechanisms may contribute to the develop-
ment of arrhythmias in sleep apnoea [120]. In animal
studies as well as clinical observations, the negative tho-
racic pressure during obstructive respiratory events in par-
ticular was identified as the most relevant factor for the
perpetuation and initiation of AF. Negative thoracic pres-
sure changes result in increased occurrence of atrial pre-
mature contractions, potentially triggering AF episodes
[121, 122]. In a pig model of OSA, application of negative
tracheal pressure during tracheal occlusion, but not tracheal
occlusion without applied negative tracheal pressure, re-
producibly and reversibly shortened the atrial refractory
period and strongly enhanced the inducibility of AF. These
arrhythmogenic electrophysiological changes were mainly
driven by a combined sympatho-vagal activation as it could
be modulated by sympathetic as well as by vagal inhibition
[61, 121, 122]. Additionally, repetitive obstructive respi-
ratory events resulted in an arrhythmogenic structural sub-
strate for AF characterised by local conduction disturbances
due to increased atrial fibrosis formation and distribution of
connexins in a rat model of sleep apnoea [123]. OSA sub-
stantially limits antiarrhythmic treatment strategies in AF
patients. For example, the effectiveness of antiarrhythmic
drugs for the treatment of AF is reduced in patients with
severe OSA [124]. Additionally, recurrence of AF after
initially effective electrical cardioversion is increased in
patients with OSA [125]. Data from a meta-analysis re-
ported that the risk ratio for recurrent AF after pulmonary
vein isolation was 1.25 in patients with versus without OSA
[126]. The risk was significantly higher (risk ratio 1.40) if
OSA had been diagnosed using polysomnography, but not
(risk ratio 1.07) if OSA was diagnosed on the basis of the
Berlin questionnaire [126], meaning that the Berlin ques-
tionnaire is not an appropriate screening or assessment tool
in this setting. Prevention of obstructive respiratory events
in OSA using CPAP reduces the risk of AF recurrence after
ablation therapy [127]. In a larger study (n = 426) [128],
CPAP therapy in patients with OSA and AF undergoing
pulmonary vein isolation was associated with a higher AF-
free survival rate (71.9 vs 36.7 % in untreated patients) and
almost similar to a group of patients without OSA. Inter-
estingly, the effect of CPAP in patients without pulmonary
vein ablation was comparable to the effect of pulmonary
vein isolation in CPAP non-user OSA patients [128]. The
proportion of patients who were free of AF without drug
treatment or repeat ablation was also significantly higher in
CPAP users versus non-users [128]. In AF management
guidelines, OSA is mentioned as being associated with AF
and as a factor contributing to a reduction in the success of
ablation procedures [129].
Ventricular arrhythmias
An AHI of [20/h was a significant and independent risk
factor for incident sudden cardiac death in a study of more
than 10,000 patients referred for polysomnography [130].
Co-existing HF and SDB increase the risk of developing
malignant ventricular arrhythmias [131]. Severe OSA also
increases the risk of ventricular premature beats and non-
sustained ventricular tachycardias (NSVT), and nocturnal
sudden cardiac death [132, 133]. It has been shown that an
episode of AF or NSVT was almost 18 times more likely to
occur within 90 s of an apnoea or hypopnoea compared
with normal breathing [134]. Registry data show that
treatment of CSR with ASV in HF patients with im-
plantable cardioverter defibrillator devices (ICDs) de-
creases the use of defibrillatory therapies, and improves
cardiac function and respiratory stability [135].
Sleep-disordered breathing and coronary artery
disease
Stable coronary artery disease
The prevalence of OSA in patients with CAD is high (up to
87 % in CAD patients referred for coronary artery bypass
graft surgery), and is significantly increased compared with
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healthy controls [136–141]. In a cohort of patients who had
undergone revascularisation for CAD, the prevalence of
OSA was higher than that of obesity, hypertension, diabetes
and AF [142]. CAD patients with OSA are not usually
sleepy, and OSA remains a significant risk factor for CAD
even after controlling for other well-known cardiovascular
risk factors, including body mass index, hypertension, hy-
percholesterolaemia, diabetes and smoking [143]. Data
from the Sleep Heart Health Study showed that men aged
40–70 years with an AHI of C30/h were 68 % more likely
to develop CAD than those with an AHI \5/h [74]. It has
also been shown that CAD patients with versus without
OSA have a higher frequency of noncalcified/mixed
atherosclerotic plaques, along with more serious stenosis
and higher number of affected vessels [144]. In addition,
OSA has been associated with nocturnal ST segment
changes, even in the absence of documented coronary artery
disease (CAD) [145]. In a prospective study of patients with
CAD, the relative increases in the risk of a composite
endpoint of death, cerebrovascular events and myocardial
infarction in patients with a desaturation index of C5/h and
an AHI of C10/h were 70 and 63 %, respectively, over
5 years of follow-up [146]. Despite all this, OSA remains an
undiagnosed problem in patients with CAD [147].
Acute coronary syndromes
In the several days after an acute myocardial infarction (MI),
the prevalence of moderate-to-severe sleep apnoea (AHI
C15/h) was as high as 55 % [148]. In addition, AHI has been
shown to be independently associated with less myocardial
salvage and a larger infarct size at 3 months [149], and the
presence of OSA inhibits recovery of left ventricular func-
tion after MI [141]. In the acute setting, the presence of OSA
was shown to be an independent predictor of cardiovascular
events in patients with non-ST-elevation coronary syn-
dromes (odds ratio [OR] 3.4; 95 % confidence interval [CI]
1.3–9.0; p = 0.0002) [150]. Cardiovascular event rates over
a 5-year follow-up were 37.5 and 9.3 % in CAD patients
with versus without OSA (p = 0.018), and the respiratory
disturbance index was identified as a significant independent
predictor of cardiovascular mortality [151]. Similar results
were reported in another study in patients with acute coro-
nary syndromes that had a mean follow-up of 227 days,
except it was OSA that was identified as independent pre-
dictor of major cardiac events (hazard ratio [HR] 11.62,
95 % CI 2.17–62.24; p = 0.004) [152].
Treatment
Treatment of OSA with CPAP can alleviate nocturnal is-
chaemia, and has been shown to have a beneficial effect on
cardiovascular event rates and mortality [153–156]. The
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Clin Res Cardiol
ongoing ISAACC (NCT01335087) [157] and TEAM ASV-
I (NCT02093377) studies will help to better define the role
of early PAP therapy in patients with acute coronary
syndromes.
Lifestyle modifications and sleep-disordered
breathing
Even if prescribed non-invasive respiratory support, pa-
tients with SDB should be screened for factors that can
exacerbate the condition, such as obesity or alcohol con-
sumption. Alcohol consumption is associated with elevated
morning blood pressure [158]. In addition, alcohol con-
sumption prior to bedtime has been associated with an in-
crease in the number and duration of apnoeas and
hypopneas in adults who snore or have SDB [159, 160],
requiring higher levels of CPAP to prevent these SDB
events [161].
Excess weight is also associated with SDB [162] and
may be complicated by obesity hypoventilation syndrome.
Obesity hypoventilation syndrome is usually diagnosed in
patients who have daytime alveolar hypoventilation
(awake, sea-level, arterial pCO2 [45 mmHg) and a body
mass index (BMI) C30 kg/m2 in the absence of other
causes of hypoventilation. The exact prevalence of obesity
hypoventilation syndrome among OSA patients is un-
known but may range from 4 to 50 % [163]. Both bariatric
surgery and non-surgical weight loss may have significant
beneficial effects on OSA via reductions in BMI and AHI.
However, bariatric surgery is often associated with greater
reductions in BMI and AHI than non-surgical alternatives
[164]. Aggressive risk factor management, including
weight reduction and reducing or eliminating alcohol in-
take is likely to reduce some SDB symptoms and could
therefore contribute to a reduction in cardiovascular com-
plications [165, 166].
Concluding remarks
Obstructive sleep apnoea represents an independent risk
factor for the development and progression of various
CVD. OSA as well as CSA/CSR are highly prevalent in
cardiac patients and worsen underlying CVD. Screening
for SDB in patients with CVD provides important infor-
mation and ongoing as well as future studies in cardio-
vascular patients should evaluate the effects of effective
treatment of SDB on mortality, quality of life, and
healthcare costs.
Acknowledgments D. L. is supported by HOMFOR 2013/2014, the
Else Kröner-Fresenius Foundation and the Deutsche Gesellschaft für
Kardiologie. Medical writing support was provided by Nicola Ryan,
Clin Res Cardiol
independent medical writer, on behalf of ResMed. MRC’s salary is
supported by the NIHR Cardiovascular Biomedical Research Unit at
the Royal Brompton Hospital, London.
Conflict of interest None.
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